of wound bed preparation — TISSUE — which formed the &#39;T&#39; of the TIME acronym. More recent retrospective analysis of large randomised pivotal clinical trials of topical wound treatments found centres where patients were debrided more frequently and which were associated with higher rates of wound closure for both chronic venous leg ulcers and diabetic foot ulcers[8]

.

Biofilms As described in more detail in the next section, recent data has revealed that wound debridement plays a very important role in reducing the levels of bacterial biofilms, which are tightly attached to components of the extracellular matrix of chronic wound beds, to the surfaces of bones (osteomyelitis), or to the surfaces of orthopaedic implants[9]

.

Thus, debridement (mechanical or surgical) of devitalised tissues and bacterial biofilms has become a &#39;must-do&#39; component of wound bed preparation, which is essential for effective management of chronic wounds. Recent advances have also further emphasised that wound debridement is a vital component of wound bed preparation[10]

to propose the acronym of DIME to emphasise the benefit of frequent wound debridement.

Infection/inflammation — I It had been recognised for centuries that infection and excessive inflammation could impair healing and, prior to the 1990s, some general knowledge existed about how this took place. For example, it was known that many bacteria synthesise exotoxin and endotoxin molecules that were toxic to wound cells. However, in the 1990s more thorough biochemical analyses of acute and chronic wound fluids began to discover major differences in key molecular regulators of wound healing, especially the elevated levels of proteases (matrix metalloproteinases [MMPs]) and neutrophil elastase[11,12]

. The

persistently elevated levels of proteolytic activity in chronic wound fluids were linked to the destruction of essential growth factors, their receptors and extracellular matrix proteins[13]

. Furthermore, healing of chronic

wounds was found to be depressed in wounds that had high levels of MMP activity[14]

. Clearly,

reduction of infection and inflammation was a major concept that needed to be incorporated into wound bed preparation[15]

. This increased understanding of the link

between infection and inflammation and elevated levels of proteases in chronic wound beds led to the eventual development of dressings that contain collagen fibres. These fibres serve as &#39;sacrificial substrates&#39; that are then &#39;chewed up&#39; (degraded) by the elevated proteases in chronic wound fluids, which dramatically reduces the proteolytic damage to proteins that are essential for healing like growth factors, receptors and extracellular matrix proteins in the wound bed[16] Complementing the development of

.

dressings that reduce protease activities is the recent development of rapid, point-of- care detectors that assess the levels of active MMPs in wound fluids. Even more advanced rapid point-of-care detectors that can simultaneously measure multiple biomarkers of healing in wound fluids or serum are currently under development. Another recent discovery that reinforced the importance of limiting infection and inflammation in wound beds was the discovery that a majority (~60%) of chronic wounds contained bacterial biofilms[17]

. Bacteria in . This led some groups

mature biofilm communities are extremely tolerant to antibodies and reactive oxygen species (ROS) generated by inflammatory cells, as well as to systemic antibiotics and topical antimicrobial agents, including silver and polyhexamethylene biguanide (PHMB, which normally kill planktonic bacteria (single cells) very effectively[18]

. Thus, removing mature

biofilms that are tightly attached to wound bed components by debridement is the best option to rapidly reduce biofilms in chronic wounds. However, clinical studies show that biofilms can fully reform within 48–72 hours after effective debridement of chronic wounds if effective bacterial barrier dressings are not applied straightaway[19]

.

Moisture Balance — M Establishing the optimal balance of moisture in the wound bed has dramatic effects on the healing of open wounds, yet it is one of the most challenging aspects of TIME for clinicians to physically manage. This is because the amount of exudate produced by wounds can change substantially over a few days and it has a significant impact on patients&#39; well being and quality of life. Clinicians using the TIME framework are more

likely to understand the need to address the underlying cause of the problem[20]

, for example,

a clinician trained in the principles of wound bed preparation and TIME is more likely to

Page Points

1. Increased understanding of the link between infection and inflammation and elevated levels of proteases in chronic wound beds led to the eventual development of dressings that contain collagen fibres

2. Another recent discovery that reinforced the importance of limiting infection and inflammation in wound beds was the discovery that a majority (~60%) of chronic wounds contained bacterial biofilms

3. Complementing the development of dressings that reduce protease activities is the recent development of rapid, point- of-care detectors that assess the levels of active MMPs in wound fluids

References

4. Falanga V. Wound bed preparation and the role of enzymes: a case for multiple actions of therapeutic agents.Wounds 2002; 14(2): 47–57.